Biodegradable polymers can be used as bases for pharmaceutical preparations such as microcapsules. Such a biodegradable polymer is disclosed in Japanese Kokai Patent Application No. 61-28521 (the corresponding U.S. Pat. Nos. 4,677,191 and 4,683,288) which teaches that the polycondensation reaction of tactic acid and/or glycolic acid, in the presence or absence of a catalyst, gives rise to such a polymer or copolymer.
Japanese Patent publication No. 1-57087 (the corresponding U.S. Pat. Nos. 4,652,441, 4,711,782 and 4,917,893) discloses a method of manufacturing sustained-releasing microcapsules employing such biodegradable polymers.
Japanese Kokai Patent publication No. 62-54760 (the corresponding U.S. Pat. Nos. 4,728,721 and 4,849,228) mentions that the initial drug release Pattern of microcapsules can be improved by washing a biodegradable polymer solution with water to remove the water-soluble low molecular fraction.
Japanese Kokai Patent publication No. 2-212436 describes a prolonged release pharmaceutical polymer available on direct dehydrative polycondensation of lactic acid and/or glycolic acid with a hydroxycarboxylic acid.
In a prolonged release preparation comprising a dispersion of a drug substance in a biodegradable macromolecular compound, it is preferable that the rate of drug release can be controlled as desired. Generally the period of release of such a prolonged release preparation is controlled by adjusting the monomer composition and molecular weight of the biodegradable polymer used for the preparation. The rate of d-rug release is preferably constant over the entire period of release. As mentioned hereinbefore, many proposals have been made for improving the initial release Pattern of this type of preparation. However, when the designed release period is comparatively short, it is frequently encountered that the drug is released encased in the second half of the release period. Furthermore, the composition and molecular weight of the biodegradable polymer must be optimized for each drug used and each designed release period and this optimization requires much time and effort.
Furthermore, it is difficult to obtain a constant drug release Pattern by using a preparation mixing two kinds of microcapsule which have different release periods, since the drug release Pattern of the mixed preparation is apt to change discontinuously in the course of the drug release.
The inventors of the present invention explored into this field of technology for overcoming the above-mentioned disadvantages and found that when the period of drug release is controlled using a simple blend of a biodegradable polymer having a comparatively low degradation rate and a biodegradable polymer having a comparatively high degradation rate, the release characteristic of the system in the second half of the release period is remarkably improved over that of a system employing a copolymer of the same monomer composition. The present invention is predicated on the above finding.